PF-06273340

PF-06273340 is a peripherally restricted pan-Trk inhibitor with IC₅₀ values of 6, 4, 3 nM for TrkA, TrkB, and TrkC receptors. PF-06273340 binds in a DFG-out conformation, targeting less conserved kinase ligand binding domain regions outside the ATP binding pocket. PF-06273340 exhibits anti-hyperalgesic and analgesic effects. PF-06273340 can be used for the research of pain^[1][2]. In Vitro:PF-06273340 potently inhibits TrkA, TrkB, and TrkC kinases with IC₅₀ values of 6 nM, 4 nM, and 3 nM, respectively^[1].
PF-06273340 exhibits low metabolic turnover in human liver microsomes, with a rate of <8.0 μL/min/mg protein^[1].
PF-06273340 is a good substrate for P-glycoprotein, as demonstrated by an efflux ratio of 35.7 in the MDCK-MDR1 assay^[1].
PF-06273340 is a substrate for BCRP, as demonstrated by an efflux ratio of 4.0^[1].
PF-06273340 (1 μM) is highly kinase-selective, potently inhibiting only MUSK (IC₅₀ = 53 nM), FLT-3 (IC₅₀ = 395 nM), IRAK1 (IC₅₀ = 2.5 μM), MKK (90% at 1 μM), and DDR1 (60% at 1 μM) among 309 tested kinases^[1].
PF-06273340 has no measurable activity at the hERG channel, with an IC₅₀ >30.0 μM^[1].
PF-06273340 exhibits minimal cytotoxicity in THLE cells (IC₅₀ >42 μM) and HepG2 cells (IC₅₀ >300 μM)^[1].